We measured arteriovenous (a-v) differences in concentrations of tumor necrosis factor-( (TNF() and interluekin-6 (IL-6) across a subcutaneous adipose tissue bed in the post-absorptive state in 39 subjects 31.8 [22.3-38.7}kg.m-2; percent body fat 28.7 {17.6-50.7}%). Glycerol release from fat cells can be studied by stable isotope dilution mass spectrometry and is a marker of lipolysis. A sub-group of 8 subjects had a-v differences measured across forearm muscle. Thirty subjects were studied from late morning to early evening - 19 ate a high carbohydrate meal around 1300 hr.; 11 continued to fast. We found a greater than two-fold increase in IL-6 concentrations across the adipose tissue bed (arterial 2.27 {1.42-3.53} pg.ml-1; venous 6.71 {3.36-9.62} pg.ml-1, p<0.001), but not across forearm muscle. Arterial plasma concentrations of IL-6 correlated significantly with BMI and percent body fat. Subcutaneous adipose tissue IL-6 production increased by the early evening both in subjects who had extended their fasting and in subjects who had eaten. Neither deep forearm nor subcutaneous adipose tissue consistently released TNF(. Although both IL-6 and TNF( are expressed by adipose tissue, our results show that there are important differences in their systemic release. TNF( is not released by this subcutaneous depot. In contrast IL-6 is released from the depot, and is thereby able to signal systemically.